Our objectives are to elaborate the nature of the cellular defects giving rise to autioimmune and lymphoproliferative neoplastic diseases, using the NZB, BXSB, PN, MRL/1pr and MRL/plus plus mouse strains as models. Hemopoietic stem cell hyperactivity is a common denominator of disease in these strains and may have an etiologic relationship. Stem cell self-renewal capacities will be determined for these strains to see if proliferative potential is abnormal in these models. In related studies, radiation chimeras composed of second to fourth passaged stem cells from autioimmune and control strains will be examined for immune and autoimmune capacities and leukemogenic risk as a function of stem cell content and proliferative capacity.